Choline Transporter Immunohistochemistry

Acetylcholinesterase enzymatic histochemistry (AChE EHC), which highlights abnormal cholinergic nerves in the mucosa of aganglionic bowel, has been used for decades to evaluate rectal biopsies for Hirschsprung disease (HSCR). While useful diagnostically, AChE EHC is not compatible with conventional formalin-fixed and paraffin-embedded (FFPE) tissues and is not widely available. The choline transporter (ChT) is a putative alternative marker of cholinergic nerves. ChT immunohistochemistry (IHC) was investigated using FFPE biopsies and resections from patients with confirmed HSCR, as well as appropriate non-HSCR controls. ChT immunostaining was effective at identifying cases with HSCR and qualitatively similar to AChE EHC on frozen section. Among 3 pathologists, the diagnostic positive and negative predictive values based on ChT IHC ranged from 0.84–0.94 and 0.85–0.89, respectively, with good inter-observer agreement (Cohen kappa = 0.70–0.90). ChT IHC was useful in unusual scenarios in which calretinin (CR) IHC failed to correctly identify patients with HSCR. In 10 cases of short-segment HSCR, abnormal ChT+ mucosal innervation was present through the entire aganglionic segment and into portions of the TZ with submucosal nerve hypertrophy. In contrast, mucosal CR IHC was retained in the TZ and adjacent aganglionic bowel, which could lead to misinterpretation of a biopsy as ganglionic bowel. Indeed, 6 such patients were identified with paradoxical CR-positive mucosal innervation in their diagnostic biopsies. ChT IHC was interpreted as unequivocal HSCR in these cases, and HSCR was confirmed on resection. In summary, ChT IHC in FFPE tissue demonstrates high positive and negative predictive values for HSCR, is superior to CR IHC in a subset of cases, and can be incorporated into routine practice without the need for specialized techniques.

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Are We Underdiagnosing Hirschsprung Disease?

Pediatric and Developmental Pathology ◽

10.1177/1093526619889434 ◽

2019 ◽

Vol 23 (1) ◽

pp. 60-71

Author(s):

Raj P Kapur ◽

Lusine Ambartsumyan ◽

Caitlin Smith

Keyword(s):

Transition Zone ◽

Ganglion Cells ◽

Hirschsprung Disease ◽

Rectal Biopsy ◽

Cholinergic Innervation ◽

Short Segment ◽

Recent Improvement ◽

Recent Trends ◽

Mucosal Innervation ◽

Rectal Biopsies

Hirschsprung disease (HSCR) is conventionally defined as aganglionosis of the distal rectum and a variable length of proximal contiguous bowel with a transition zone of ganglionic, but neuroanatomically abnormal, bowel located immediately upstream. Recent improvement in our understanding of the pathology and genetics of HSCR and relevant animal models indicates highly variable expressivity. The spectrum of intestinal neuropathology includes patients with very short-segment aganglionosis, limited to the distal 1 to 2 cm of the rectum, and possibly patients with no true aganglionic segment, but nonphysiological transition zone pathology in their distal rectums. The presence or absence of submucosal ganglion cells in a rectal biopsy is not sufficient to exclude these patients, in whom submucosal nerve hypertrophy and/or abnormal cholinergic mucosal innervation may be the only diagnostic clues. In addition, diagnosis or exclusion of HSCR by rectal biopsy now relies in part on mucosal patterns of calretinin immunohistochemistry, with less emphasis on submucosal tissue adequacy and assessment of cholinergic innervation. These recent trends in the surgical pathology approach to rectal biopsies may miss patients at the phenotypically milder end of the malformation spectrum, with profound implications for subsequent management, prognosis, and genetic counseling.

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Multi-Slice Computed Tomographic Angiography for Stenosis Detection in Forearm Hemodialysis Arteriovenous Fistulas

The Journal of Vascular Access ◽

10.1177/112972980800900409 ◽

2008 ◽

Vol 9 (4) ◽

pp. 278-284 ◽

Cited By ~ 13

Author(s):

P.P.G.M. Rooijens ◽

G.P Serafino ◽

D. Vroegindeweij ◽

R. Dammers ◽

T.I. Yo ◽

...

Keyword(s):

High Specificity ◽

Computed Tomographic Angiography ◽

Observer Agreement ◽

Predictive Values ◽

Computed Tomographic ◽

Arteriovenous Fistulas ◽

Blinded Manner ◽

Sensitivity Specificity ◽

Tomographic Angiography ◽

Diameter Reduction

Purpose A method of diagnosing the extent and severity of arteriovenous fistula (AVF) stenoses is multi-slice computed tomographic angiography (MS-CTA). The aim of this prospective study was to assess the accuracy of MS-CTA for the detection and grading of stenoses in AVF in comparison to digital subtraction angiography (DSA), which was used as the gold standard of reference. Methods Fifteen hemodialysis (HD) patients with dysfunctioning forearm AVF were included. These AVFs were evaluated by both DSA and MS-CTA and were read in a prospective, blinded manner by two radiologists experienced in vascular imaging. Results ROC analysis revealed areas under the curve of 0.90 ± 0.07 for observer I and 0.87 ± 0.08 for observer II at a stenosis cut-off level of ≥50% diameter reduction. The combined results for MS-CTA showed sensitivity, specificity and positive and negative predictive values of 82%, 98%, 82% and 98% for stenoses ≥50% and 71%, 99%, 77% and 98% for stenoses ≥75%. Inter-observer agreement for the detection of stenoses ≥50% diameter reduction was 0.70 and 1.0, for MS-CTA and DSA, respectively. Conclusion MS-CTA can provide good visualization of forearm HD access AVF and has moderate sensitivity, but high specificity for the detection of flow-limiting stenoses.

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Inter-observer agreement on the evaluation of automated breast volume scanner for breast masses

Traditional Medicine and Modern Medicine ◽

10.1142/s2575900021500026 ◽

2022 ◽

pp. 1-11

Author(s):

Yingchun Liu ◽

Lin Chen ◽

Jia Zhan ◽

Xuehong Diao ◽

Yun Pang ◽

...

Keyword(s):

Imaging Modality ◽

Observer Agreement ◽

Breast Volume ◽

Imaging Data ◽

Predictive Values ◽

Breast Masses ◽

Cutoff Value ◽

Automated Breast Volume Scanner ◽

The Masses ◽

Sensitivity Specificity

Objective: To explore inter-observer agreement on the evaluation of automated breast volume scanner (ABVS) for breast masses. Methods: A total of 846 breast masses in 630 patients underwent ABVS examinations. The imaging data were independently interpreted by senior and junior radiologists regarding the mass size ([Formula: see text][Formula: see text]cm, [Formula: see text][Formula: see text]cm and total). We assessed inter-observer agreement of BI-RADS lexicons, unique descriptors of ABVS coronal planes. Using BI-RADS 3 or 4a as a cutoff value, the diagnostic performances for 331 masses with pathological results in 253 patients were assessed. Results: The overall agreements were substantial for BI-RADS lexicons ([Formula: see text]–0.779) and the characteristics on the coronal plane of ABVS ([Formula: see text]), except for associated features ([Formula: see text]). However, the overall agreement was moderate for orientation ([Formula: see text]) for the masses [Formula: see text][Formula: see text]cm. The agreements were substantial to be perfect for categories 2, 3, 4, 5 and overall ([Formula: see text]–0.918). However, the agreements were moderate to substantial for categories 4a ([Formula: see text]), 4b ([Formula: see text]), and 4c ([Formula: see text]), except for category 4b of the masses [Formula: see text][Formula: see text]cm ([Formula: see text]). Moreover, for radiologists 1 and 2, there were no significant differences in sensitivity, specificity, accuracy, positive and negative predictive values with BI-RADS 3 or 4a as a cutoff value ([Formula: see text] for all). Conclusion: ABVS is a reliable imaging modality for the assessment of breast masses with good inter-observer agreement.

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Experience with a Dynamic Inexpensive Video-Conferencing System for Frozen Section Telepathology

Analytical Cellular Pathology ◽

10.1155/2000/908426 ◽

2000 ◽

Vol 21 (3-4) ◽

pp. 169-175 ◽

Cited By ~ 18

Author(s):

J. P. A. Baak ◽

P. J. van Diest ◽

G. A. Meijer

Keyword(s):

Image Quality ◽

Frozen Section ◽

Video Conferencing ◽

Final Diagnosis ◽

Complete Agreement ◽

Frozen Sections ◽

Predictive Values ◽

Video Conferencing System ◽

Frozen Section Diagnosis ◽

Conferencing System

Aim: To evaluate the feasibility of an inexpensive, generally applicable video‐conferencing system for frozen section telepathology (TP).Methods: A commercially widely available PC‐based dynamic video‐conferencing system (PictureTel LIVE, model PCS 100) has been evaluated, using two, four and six ISDN channels (128–384 kilobits per second (kbs)) bandwidths. 129 frozen sections have been analyzed which were classified by TP as benign, uncertain (the remark probably benign, or probably malignant was allowed), malignant, or not acceptable image quality. The TP results were compared with the original frozen section diagnosis and final paraffin diagnosis.Results: Only 384 kbs (3 ISDN‐2 lines) resulted in acceptable speed and quality of microscope images, and synchronous image/speech transfer. In one of the frozen section cases (0.7%), TP image quality was classified as not acceptable, leaving 128 frozen sections for the analysis. Five of these cases were uncertain by TP, and also deferred by frozen section procedure (FS). One more benign and three malignant FS cases were classified as uncertain by TP. Three additional cases were uncertain by FS, but benign according to TP (in agreement with the final diagnosis). In one case, FS diagnosis was uncertain but TP was malignant (in agreement with the final diagnosis). Thus, test efficiency (i.e., cases with complete agreement) was 120/128 (93.8%, Kappa = 0.88) between FS and TP. Sensitivity was 93.5%, specificity 98.6%, positive and negative predictive values were 97.7% and 96.0%. Between TP and final diagnosis agreement was even higher. More importantly, there was not a single discrepancy as to benign‐malignant. Moreover, there was a clear learning effect: 5 of the 8 FS/TP discrepancies occurred in the first 42 cases (5/42=11.9%), the remaining 3 in the following 86 cases (3/86=3.5%).Discussion: The results are encouraging. However, TP evaluation is time‐consuming (5–15 min for one case instead of 2–4 min although speed went up with more experience) and is more tiring. The system has the following technical drawbacks: no possibility to point at objects or areas of interest in the life image at the other end, resolution (rarely) may become suboptimal (blocky), storage of images evaluated (which is essential for legal reasons) is not easy and no direct control of a remote motorized microscope. Yet, all users were positive about the system both for telepathology and personal contact by video‐conferencing. Conclusion: With a relatively simple videoconferencing system, accurate dynamic telepathology frozen section diagnosis can be obtained without false positive or negative results, although a limited number of uncertain cases will have to be accepted.

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Ovarian Frozen Section Diagnosis: Use of Whole-Slide Imaging Shows Excellent Correlation Between Virtual Slide and Original Interpretations in a Large Series of Cases

Archives of Pathology & Laboratory Medicine ◽

10.5858/2009-0320-oa.1 ◽

2010 ◽

Vol 134 (7) ◽

pp. 1020-1023 ◽

Cited By ~ 4

Author(s):

Margaret A. Fallon ◽

David C. Wilbur ◽

Manju Prasad

Keyword(s):

Frozen Section ◽

Virtual Slide ◽

Granulosa Cell Tumor ◽

Routine Practice ◽

Corpora Lutea ◽

Operating Characteristics ◽

Frozen Section Diagnosis ◽

Very High ◽

Whole Slide Images

Abstract Context.—Whole-slide images (WSI) are a tool for remote interpretation, archiving, and teaching. Ovarian frozen sections (FS) are common and hence determination of the operating characteristics of the interpretation of these specimens using WSI is important. Objectives.—To test the reproducibility and accuracy of ovarian FS interpretation using WSI, as compared with routine analog interpretation, to understand the technology limits and unique interpretive pitfalls. Design.—A sequential series of ovarian FS slides, representative of routine practice, were converted to WSI. Whole-slide images were examined by 2 pathologists, masked to all prior results. Correlation characteristics among the WSI, the original, and the final interpretations were analyzed. Results.—A total of 52 cases, consisting of 71 FS slides, were included; 34 cases (65%) were benign, and 18 cases (35%) were malignant, borderline, and of uncertain potential (9 [17%], 7 [13%], and 2 [4%] of 52 cases, respectively). The correlation between WSI and FS interpretations was 96% (50 of 52) for each pathologist for benign versus malignant, borderline, and uncertain entities. Each pathologist undercalled 2 borderline malignant cases (4%) as benign cysts on WSI. There were no overcalls of benign cases. Specific issues within the benign and malignant groups involved endometriosis versus hemorrhagic corpora lutea, and granulosa cell tumor versus carcinoma, respectively. Conclusions.—The correlation between original FS and WSI interpretations was very high. The few discordant cases represent recognized differential diagnostic issues. Ability to examine gross pathology and real-time consultation with surgeons might be expected to improve performance. Ovarian FS diagnosis by WSI is accurate and reproducible, and thus, remote interpretation, teaching, and digital archiving of ovarian FS specimens by this method can be reliable.

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Accuracy of Intraoperative Examination in Central Nervous System Lesions: A Study of 133 Cases

Acta Cytologica ◽

10.1159/000495175 ◽

2019 ◽

Vol 63 (3) ◽

pp. 224-232

Author(s):

Ludmila Barbosa de Souza Balsimelli ◽

Jamille Costa de Oliveira ◽

Flora Ávila Adorno ◽

Clarissa Almeida Brites ◽

Giuliano Stefanello Bublitz ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Frozen Section ◽

Final Diagnosis ◽

World Health ◽

Histopathological Diagnosis ◽

Low Grade ◽

Predictive Values ◽

Health Organization ◽

Cns Lesions

Objective: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions. Study Design: Retrospective analysis of intraoperative examination of CNS lesions and their final diagnosis obtained during 16 consecutive years. All diagnoses were reviewed and classified according to World Health Organization (WHO) grading for CNS tumors. Squash was performed in 119 cases, while frozen section and both methods were done in 7 cases each. Results: Among the 133 intraoperative examinations considered, 114 (85.7%) presented concordance and 19 (14.3%) diagnostic disagreement when compared with subsequent histopathological examinations. The sensitivity and specificity for the detection of neoplasia in intraoperative examination was 98 and 94%, respectively. The positive and negative predictive values were 99 and 88%, respectively. The accuracy for neoplastic and nonneoplastic disease was 85.7%. Disagreements were more frequent among low-grade (WHO grades I and II) neoplasms and nonmalignant cases. Conclusions: Our results showed good accuracy of the intraoperative assessments for diagnosis of CNS lesions, particularly in high-grade (grades III and IV) lesions and metastatic neoplasms.

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Normal spirometry predictive values for the Western Indian adult population

European Respiratory Journal ◽

10.1183/13993003.02129-2019 ◽

2020 ◽

Vol 56 (3) ◽

pp. 1902129

Author(s):

Dhiraj Agarwal ◽

Richard A. Parker ◽

Hilary Pinnock ◽

Sudipto Roy ◽

Deesha Ghorpade ◽

...

Keyword(s):

Lung Function ◽

Adult Population ◽

Additive Model ◽

Forced Expiratory Volume ◽

Routine Practice ◽

Generalised Additive Model ◽

Predictive Values ◽

Reference Equations ◽

Predicted Values ◽

Severity Of The Disease

Interpretation of spirometry involves comparing lung function parameters with predicted values to determine the presence/severity of the disease. The Global Lung Function Initiative (GLI) derived reference equations for healthy individuals aged 3–95 years from multiple populations but highlighted India as a “particular group” for whom further data are needed. We aimed to derive predictive equations for spirometry in a rural Western Indian adult population.We used spirometry data previously collected (2008–2012) from 1258 healthy adults (aged 18 years and over) by the Vadu Health and Demographic Surveillance System. We constructed sex-stratified prediction equations for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC using the Generalised Additive Model for Location, Scale and Shape (GAMLSS) method to derive the best fitting model of each outcome as a function of age and height.When compared with GLI Ethnicity Codes 1 (White Caucasian) and 5 (Other/Mixed), the Western Indian adult population appears to have lower lung volumes on average, though the FEV1/FVC ratio is comparable. Both age and height were predictive of mean FEV1 and FVC; and for females, the variability of response was also dependent on age. FEV1/FVC appears to have a very strong age effect, highlighting the limitations of using a fixed 0.7 cut-off value.The use of GLI normal values may result in overdiagnosis of lung disease in this population. We recommend that the values and equations generated from this study should be used by physicians in their routine practice for diagnosing disease and its severity in adults from the Western Indian population.

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An assessment of the accuracy of contrast enema for the diagnosis of Hirschsprung disease at a South African tertiary hospital

South African Journal of Radiology ◽

10.4102/sajr.v21i1.1093 ◽

2017 ◽

Vol 21 (1) ◽

Author(s):

Monica S. Msomi ◽

Hansraj Mangray ◽

Vicci Du Plessis

Keyword(s):

Diagnostic Accuracy ◽

South African ◽

False Negative ◽

False Negative Rate ◽

Hirschsprung Disease ◽

Contrast Enema ◽

Initial Screening ◽

Tertiary Referral Hospital ◽

Predictive Values ◽

Picture Archiving And Communication

Objectives: To compare radiological findings with the histological diagnosis of Hirschsprung disease (HD) to establish the usefulness of contrast enema as an initial screening and diagnostic tool. To correlate accuracy of radiological diagnosis at Grey’s Hospital with international standards.Materials and methods: Systematic searches were conducted through the Picture Archiving and Communication System and the National Health Laboratory Service records for patients aged 0–12 years, with clinically suspected HD, for whom both contrast enemas and rectal biopsies were performed between 01 January 2011 and 31 August 2015 in a tertiary-level hospital. A total of 54 such patients were identified. Diagnostic accuracy levels were calculated by comparing radiological results with histology results, which is the gold standard.Results: Diagnostic accuracy of contrast enema was 78%, sensitivity was 94.4% and the negative predictive value was 95.7%. Specificity (68.8%) and positive predictive values (63%) were considerably lower. A lower false-negative rate of 5.6% was obtained at Grey’s Hospital as compared with the international reports of up to 30%.Conclusion: Contrast enema remains useful as an initial screening and diagnostic test for HD. Results of this South African tertiary referral hospital were consistent with the best international results for sensitivity of the contrast enema (approximately 80% – 88% in excluding the disease).

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Utility of Intraoperative Frozen Sections during Thyroid Surgery

International Journal of Otolaryngology ◽

10.1155/2013/496138 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 19

Author(s):

Russel Kahmke ◽

Walter T. Lee ◽

Liana Puscas ◽

Richard L. Scher ◽

Michael J. Shealy ◽

...

Keyword(s):

Predictive Value ◽

Frozen Section ◽

Case Series ◽

Follicular Neoplasm ◽

Frozen Sections ◽

Fine Needle Aspirate ◽

Retrospective Case ◽

Predictive Values ◽

Fine Needle ◽

Intraoperative Frozen Section

Objective. To describe the usefulness of intraoperative frozen section in the diagnosis and treatment of thyroid nodules where fine needle aspirate biopsies have evidence of follicular neoplasm.Study Design. Retrospective case series.Methods. All patients have a fine needle aspirate biopsy, an intraoperative frozen section, and final pathology performed on a thyroid nodule after initiation of the Bethesda System for Reporting Thyroid Cytopathology in 2009 at a single tertiary referral center. Sensitivity, specificity, positive predictive value, and negative predictive value are calculated in order to determine added benefit of frozen section to original fine needle aspirate data.Results. The sensitivity and specificity of the frozen section were 76.9% and 67.9%, respectively, while for the fine needle aspirate were 53.8% and 74.1%, respectively. The positive and negative predictive values for the fine needle aspirates were 25% and 90.9%, respectively, while for the frozen sections were 27.8% and 94.8%, respectively. There were no changes in the operative course as a consequence of the frozen sections.Conclusion. Our data does not support the clinical usefulness of intraoperative frozen section when the fine needle aspirate yields a Bethesda Criteria diagnosis of follicular neoplasm, suspicious for follicular neoplasm, or suspicious for malignancy at our institution.

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